ArticleNature chemical biology2018
How many human proteoforms are there?
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In one paragraph
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 493 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
493citing papers in PubMed, 1 pooled it
45.0field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
493 citing papers in PubMed, 1 synthesis or guideline pooled it, 908 citations in OpenAlex.
- Proteomic profiling of pulpal and periapical diseases: a systematic review.Frontiers in dental medicine · 2026Pooled it
- Targeted proteoform degradation for precision drug design, delivery, and therapy.Drug delivery · 2026Review
- Article
- Protein rheostasis: quality control in metastable proteomes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Ketogenic Diet-Associated Remodeling of the Cortical Proteome in Rats With Genetic Absence Epilepsy.Brain and behavior · 2026Article
- Multi-omics integration of proteomics and metabolomics in pediatric health and disease.Communications medicine · 2026Review
- Direct Quantification of Complement Biomarkers Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).ACS pharmacology & translational science · 2026Article
- A Draft Map of E. coli Proteoforms.Analytical chemistry · 2026Article
- AMPK phosphorylation proceeds through hierarchical proteoform cascades revealed by integrated mass spectrometry.Science advances · 2026Article
- Large-scale single-molecule analysis of tau proteoforms.Nature methods · 2026Article
- Beyond Protein Abundance: Proteoform Diversity and Phosphoproteome Remodeling in Maize (Proteomes · 2026Review
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- Analysis of Osteocalcin Hormone Proteoforms with Vitamin D Deficiency in Patients with Diabetes Mellitus Using Multiple-Reaction Monitoring-Mass Spectrometric Immunoassay Approach.Methods and protocols · 2026Article
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Nature communications · 2026Article
- Protein Enrichment from Ascites Fluid Using Nanotrap Hydrogel Particle Technology.Journal of proteome research · 2026Article
- Chemical basis of fluorogenic substrate probe design: revisiting the past to discover the new in biochemistry.RSC chemical biology · 2026Review
- Human SRP Subunits Coordinate Protein Targeting and mRNA Quality Control.bioRxiv : the preprint server for biology · 2026Article
- Translational bottlenecks in blood-based proteomics.EMBO molecular medicine · 2026Article
- Proteomic Biomarker Discovery in Breast Cancer: Advances, Challenges, and Translational Prospects.Journal of biochemical and molecular toxicology · 2026Review
- Expanding High-Fidelity Multiplexing in Ultrasensitive Single-Molecule Protein Detection via Proximity Barcoding.Angewandte Chemie (International ed. in English) · 2026Article
433 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
53 authors at 20 institutions in 7 countries.
Ruedi AebersoldDepartment of Biology, ETH Zurich, Zürich, Switzerland.
Jeffrey N AgarDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.
I Jonathan AmsterDepartment of Chemistry, University of Georgia, Athens, Georgia, USA.ORCID 0000-0001-7523-5144
Mark S BakerDepartment of Biomedical Sciences, Macquarie University, Sydney, New South Wales, Australia.ORCID 0000-0001-5858-4035
Carolyn R BertozziDepartment of Chemistry, Stanford University, Stanford, California, USA.
Emily S BojaOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, Maryland, USA.
Catherine E CostelloDepartment of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, USA.
Benjamin F CravattDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID 0000-0001-5330-3492
Catherine FenselauDepartment of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA.
Benjamin A GarciaDepartment of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, and Epigenetics Institute, Philadelphia, Pennsylvania, USA.
Ying GeDepartment of Cell and Regenerative Biology, Human Proteomics Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jeremy GunawardenaDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Ronald C HendricksonMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Paul J HergenrotherDepartment of Chemistry, University of Illinois, Urbana, Illinois, USA.
Christian G HuberDepartment of Biosciences and Christian Doppler Laboratory for Biosimilar Characterization, University of Salzburg, Salzburg, Austria.ORCID 0000-0001-8358-1880
Alexander R IvanovDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.
Ole N JensenDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Michael C JewettThe Center for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
Neil L KelleherDepartment of Chemistry, Molecular Biosciences and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.ORCID 0000-0002-8815-3372
Laura L KiesslingDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0001-6829-1500
Nevan J KroganDepartment of Cellular Molecular Pharmacology, University of California, San Francisco, California, USA.
Martin R LarsenDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Joseph A LooDepartment of Biological Chemistry, University of California, Los Angeles, California, USA.ORCID 0000-0001-9989-1437
Rachel R Ogorzalek LooDepartment of Biological Chemistry, University of California, Los Angeles, California, USA.
Emma LundbergScience for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Michael J MacCossDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Parag MallickDepartment of Chemistry, Stanford University, Stanford, California, USA.
Vamsi K MoothaDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Milan MrksichThe Center for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
Tom W MuirDepartment of Chemistry, Princeton University, Princeton, New Jersey, USA.
Steven M PatrieDepartment of Chemistry, Molecular Biosciences and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.
James J PesaventoDepartment of Biology, Saint Mary's College of California, Moraga, California, USA.ORCID 0000-0001-6107-3666
Sharon J PitteriDepartment of Chemistry, Stanford University, Stanford, California, USA.ORCID 0000-0002-3119-873X
Henry RodriguezOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, Maryland, USA.
Alan SaghatelianSalk Institute for Biological Studies, Torrey Pines, California, USA.
Wendy SandovalApplied Proteomics, Genentech, Inc., San Francisco, California, USA.
Hartmut SchlüterDepartment of Clinical Chemistry/Central Laboratories, University Medical Center Hamburg - Eppendorf, Hamburg, Germany.ORCID 0000-0002-9358-7036
Salvatore SechiNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.
Sarah A SlavoffDepartment of Chemistry, Yale University, New Haven, Connecticut, USA.
Lloyd M SmithDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Michael P SnyderDepartment of Genetics, Stanford University, Stanford, California, USA.
Paul M ThomasDepartment of Chemistry, Molecular Biosciences and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.ORCID 0000-0003-2887-4765
Mathias UhlénDepartment of Microbiology, KTH Royal Institute of Technology, Stockholm, Sweden.
Jennifer E Van EykCedars Sinai Medical Center, Los Angeles, California, USA.
Marc VidalDepartment of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
David R WaltDepartment of Pathology, Harvard Medical School and Wyss Institute at Harvard University, Boston, Massachusetts, USA.
Forest M WhiteDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Evan R WilliamsDepartment of Chemistry, University of California, Berkeley, Berkeley, California, USA.
Therese WohlschlagerDepartment of Biosciences and Christian Doppler Laboratory for Biosimilar Characterization, University of Salzburg, Salzburg, Austria.
Vicki H WysockiDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA.
Nathan A YatesDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Nicolas L YoungVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.ORCID 0000-0002-3323-2815
Bing ZhangVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.ORCID 0000-0001-8676-2425
Northwestern University · USHarvard University · USStanford University · USBaylor College of Medicine · USCancer Clinic · USMassachusetts Institute of Technology · USNortheastern University · USUniversity of California, Los Angeles · USUniversity of Salzburg · ATUniversity of Southern Denmark · DKUniversity of Wisconsin–Madison · USAbterra Biosciences (United States) · USBoston University · USCedars-Sinai Medical Center · USETH Zurich · CHKTH Royal Institute of Technology · SEMacquarie University · AUMemorial Sloan Kettering Cancer Center · USNational Institute of Diabetes and Digestive and Kidney Diseases · USPrinceton University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MViral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8MShared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6MGenomic and Proteomic Architecture of AtherosclerosisR01HL111362 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HERRINGTON, DAVID MCLEOD · 2012 to 2021
$17.2MTR&D 7: Cell Specific ProteomicsP41GM108569 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2015 to 2024
$13.6MProtein Chemistry and ProteomicsP01HL112730 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI VAN EYK, JENNIFER E · 2013 to 2017
$12.0MViral modulation of epitranscriptomic mechanismsR01AI118891 · NIAID · WASHINGTON UNIVERSITY · PI GARCIA, BENJAMIN A, WEITZMAN, MATTHEW D. · 2015 to 2025
$5.4MUbiquitinated Proteins in Exosomes of Immune Suppressive Myeloid CellsR01GM021248 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI FENSELAU, CATHERINE C, FUSHMAN, DAVID · 1985 to 2017
$4.6MMitochondrial Turnover in the Human HeartR01HL132075 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI GOTTLIEB, ROBERTA A., VAN EYK, JENNIFER E · 2017 to 2020
$2.1MAlgorithms for Glyco-Proteoform DetectionR01GM115739 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI PATRIE, STEVEN MATTHEW · 2016 to 2020
$1.9MIntact Proteoform Identification and QuantificationR01GM114292 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GOULD, MICHAEL N, SMITH, LLOYD M · 2015 to 2018
$1.6MUnderstanding the Role of Combinatorial Histone PTM PatternsR01GM110174 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GARCIA, BENJAMIN A · 2014 to 2017
$1.3MNCI NIH HHS P01 CA196539NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014195NHLBI NIH HHS P01 HL112730NHLBI NIH HHS R01 HL111362NHLBI NIH HHS R01 HL132075NIAID NIH HHS R01 AI118891NIGMS NIH HHS P41 GM108569NIGMS NIH HHS R01 GM021248NIGMS NIH HHS R01 GM110174NIGMS NIH HHS R01 GM114292NIGMS NIH HHS R01 GM115739NIH HHS S10 OD019938
Abstract
Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
Indexed as
Genome, HumanProtein Processing, Post-TranslationalDatabases, ProteinHumansMass SpectrometryPhenotypeProtein BiosynthesisProtein IsoformsProteinsProteomeProteomicsUbiquitinProtein IsoformsProteinsProteomeUbiquitin
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